SLC12A5 encodes the neuron-specific K+-Cl- cotransporter KCC2, which serves as the major chloride extruder in mature neurons and is essential for establishing proper neuronal chloride homeostasis 1. By maintaining low intracellular chloride levels, KCC2 enables GABA and glycine receptors to mediate hyperpolarization and neuronal inhibition, making it crucial for the excitation-inhibition balance in the central nervous system 1. The protein mediates electroneutral potassium-chloride cotransport and is involved in dendritic spine development 2. KCC2 expression is developmentally regulated, with upregulation driving the postsynatal switch of GABA from excitation to inhibition 3. Loss-of-function variants in SLC12A5 have pathogenic potential for neurological disorders, particularly epilepsy and developmental encephalopathies 1. The gene produces multiple alternatively spliced transcripts that are differentially expressed in psychiatric conditions, with altered expression patterns observed in schizophrenia and major depression 3. Beyond neurological functions, SLC12A5 has been implicated in cancer biology, where it promotes tumor growth and ferroptosis resistance in hepatocellular carcinoma through ER stress mechanisms 4. Genetic variations affecting SLC12A5 expression are associated with brain structural and functional differences in healthy individuals 5.